Objectives We conducted a systematic review and meta-analysis to determine the predictive value of findings of coronary computed tomography angiography for incident cardiovascular events. Background ...Initial studies indicate a prognostic value of the technique; however, the level of evidence as well as exact independent risk estimates remain unclear. Methods We searched PubMed, EMBASE, and the Cochrane Library through January 2010 for studies that followed up ≥100 subjects for ≥1 year and reported at ≥1 hazard ratio (HR) of interest. Risk estimates for the presence of significant coronary stenosis (primary endpoint; ≥50% diameter stenosis), left main coronary artery stenosis, each coronary stenosis, 3-vessel disease, any plaque, per coronary segment containing plaque, and noncalcified plaque were derived in random effect regression analysis, and causes of heterogeneity were determined in meta-regression analysis. Results We identified 11 eligible articles including 7,335 participants (age 59.1 ± 2.6 years, 62.8% male) with suspected coronary artery disease. The presence of ≥1 significant coronary stenosis (9 studies, 3,670 participants, and 252 outcome events 6.8% with 62% revascularizations) was associated with an annualized event rate of 11.9% (6.4% in studies excluding revascularization). The corresponding HR was 10.74 (98% confidence interval CI: 6.37 to 18.11) and 6.15 (95% CI: 3.22 to 11.74) in studies excluding revascularization. Adjustment for coronary calcification did not attenuate the prognostic significance (p = 0.79). The estimated HRs for left main stenosis, presence of plaque, and each coronary segment containing plaque were 6.64 (95% CI: 2.6 to 17.3), 4.51 (95% CI: 2.2 to 9.3), and 1.23 (95% CI: 1.17 to 1.29), respectively. Conclusions Presence and extent of coronary artery disease on coronary computed tomography angiography are strong, independent predictors of cardiovascular events despite heterogeneity in endpoints, categorization of computed tomography findings, and study population.
Abstract Objectives This study sought to determine whether splenic activation after acute coronary syndrome (ACS) is linked to leukocyte proinflammatory remodeling and whether splenic activity ...independently predicts the risk of cardiovascular disease (CVD) events. Background Pre-clinical data suggest the existence of a cardiosplenic axis, wherein activation of hematopoietic tissues (notably in the spleen) results in liberation of proinflammatory leukocytes and accelerated atherosclerotic inflammation. However, it is presently unknown whether a cardiosplenic axis exists in humans and whether splenic activation relates to CVD risk. Methods18 F-fluorodeoxyglucose (18 FDG)–positron emission tomography (PET) imaging was performed in 508 individuals across 2 studies. In the first study, we performed FDG-PET imaging in 22 patients with recent ACS and 22 control subjects. FDG uptake was measured in spleen and arterial wall, whereas proinflammatory gene expression of circulating leukocytes was assessed by quantitative real-time polymerase chain reaction. In a second study, we examined the relationship between splenic tissue FDG uptake with subsequent CVD events during follow-up (median 4 years) in 464 patients who previously had undergone FDG-PET imaging. Results Splenic activity increased after ACS and was significantly associated with multiple indices of inflammation: 1) up-regulated gene expression of proinflammatory leukocytes; 2) increased C-reactive protein; and 3) increased arterial wall inflammation (FDG uptake). Moreover, in the second study, splenic activity (greater than or equal to the median) was associated with an increased risk of CVD events (hazard ratio HR: 3.3; 95% confidence interval CI: 1.5 to 7.3; p = 0.003), which remained significant after adjustment for CVD risk factors (HR: 2.26; 95% CI: 1.01 to 5.06; p = 0.04) and for arterial FDG uptake (HR: 2.68; 95% CI: 1.5 to 7.4; p = 0.02). Conclusions Our findings demonstrate increased splenic metabolic activity after ACS and its association with proinflammatory remodeling of circulating leukocytes. Moreover, we observed that metabolic activity of the spleen independently predicted risk of subsequent CVD events. Collectively, these findings provide evidence of a cardiosplenic axis in humans similar to that shown in pre-clinical studies.
Objectives The aim of this study was to evaluate whether computed tomography (CT) attenuation, as a measure of fat quality, is associated with cardiometabolic risk factors above and beyond fat ...quantity. Background Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are pathogenic fat depots associated with cardiometabolic risk. Adipose tissue attenuation in CT images is variable, similar to adipose tissue volume. However, whether the quality of abdominal fat attenuation is associated with cardiometabolic risk independent of the quantity is uncertain. Methods Participants were drawn from the Framingham Heart Study CT substudy. The VAT and SAT volumes were acquired by semiquantitative assessment. Fat quality was measured by CT attenuation and recorded as mean Hounsfield unit (HU) within each fat depot. Sex-specific linear and logistic multivariable regression models were used to assess the association between standard deviation (SD) decrease in HU and each risk factor. Results Lower CT attenuation of VAT and SAT was correlated with higher body mass index levels in both sexes. Risk factors were generally more adverse with decreasing HU values. For example, in women, per 1 SD decrease in VAT HU, the odds ratio (OR) was increased for hypertension (OR: 1.80), impaired fasting glucose (OR: 2.10), metabolic syndrome (OR: 3.65), and insulin resistance (OR: 3.36; all p < 0.0001). In models that further adjusted for VAT volume, impaired fasting glucose, metabolic syndrome, and insulin resistance remained significant. Trends were similar but less pronounced for SAT and for men. There was evidence of an interaction between HU and fat volume among both women and men. Conclusions Lower CT attenuation of VAT and SAT is associated with adverse cardiometabolic risk above and beyond total adipose tissue volume. Qualitative indices of abdominal fat depots may provide insight regarding cardiometabolic risk independent of fat quantity.
Coronary artery calcium is an accurate predictor of cardiovascular events. While it is visible on all computed tomography (CT) scans of the chest, this information is not routinely quantified as it ...requires expertise, time, and specialized equipment. Here, we show a robust and time-efficient deep learning system to automatically quantify coronary calcium on routine cardiac-gated and non-gated CT. As we evaluate in 20,084 individuals from distinct asymptomatic (Framingham Heart Study, NLST) and stable and acute chest pain (PROMISE, ROMICAT-II) cohorts, the automated score is a strong predictor of cardiovascular events, independent of risk factors (multivariable-adjusted hazard ratios up to 4.3), shows high correlation with manual quantification, and robust test-retest reliability. Our results demonstrate the clinical value of a deep learning system for the automated prediction of cardiovascular events. Implementation into clinical practice would address the unmet need of automating proven imaging biomarkers to guide management and improve population health.
The goal of this study was to assess whether a deep learning estimate of age from a chest radiograph image (CXR-Age) can predict longevity beyond chronological age.
Chronological age is an imperfect ...measure of longevity. Biological age, a measure of overall health, may improve personalized care. This paper proposes a new way to estimate biological age using a convolutional neural network that takes as input a CXR image and outputs a chest x-ray age (in years) as a measure of long-term mortality risk.
CXR-Age was developed using CXR from 116,035 individuals and validated in 2 held-out testing sets: 1) 75% of the CXR arm of PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) (N = 40,967); and 2) the CXR arm of NLST (National Lung Screening Trial) (N = 5,414). CXR-Age was compared to chronological age and a multivariable regression model of chronological age, risk factors, and radiograph findings to predict all-cause and cardiovascular mortality with a maximum 23 years and 13 years of follow-up, respectively. The primary outcome was observed mortality; results are provided for the testing datasets only.
In the PLCO testing dataset, a 5-year increase in CXR-Age carried a higher risk of all-cause mortality than a 5-year increase in chronological age (CXR-Age hazard ratio HR: 2.26 95% confidence interval (CI): 2.24 to 2.29 vs. chronological age HR: 1.77 95% CI: 1.75 to 1.78; p < 0.001). A similar pattern was found for cardiovascular mortality (CXR-Age cause-specific HR: 2.45 per 5 years 95% CI: 2.34 to 2.56 vs. chronological age HR: 1.82 per 5 years 95% CI: 1.74 to 1.90). Similar results were seen for both outcomes in the NLST external testing dataset. Adding CXR-Age to the multivariable model resulted in significant improvements for predicting both outcomes in both testing datasets (p < 0.001 for all comparisons).
Based on a CXR image, CXR-Age predicted long-term all-cause and cardiovascular mortality.
Display omitted
Objectives This study sought to determine the feasibility of performing a comprehensive cardiac computed tomographic (CT) examination incorporating stress and rest myocardial perfusion imaging ...together with coronary computed tomography angiography (CTA). Background Although cardiac CT can identify coronary stenosis, very little data exist on the ability to detect stress-induced myocardial perfusion defects in humans. Methods Thirty-four patients who had a nuclear stress test and invasive angiography were included in the study. Dual-source computed tomography (DSCT) was performed as follows: 1) stress CT: contrast-enhanced scan during adenosine infusion; 2) rest CT: contrast-enhanced scan using prospective triggering; and 3) delayed scan: acquired 7 min after rest CT. Images for CTA, computed tomography perfusion (CTP), and single-photon emission computed tomography (SPECT) were each read by 2 independent blinded readers. Results The DSCT protocol was successfully completed for 33 of 34 subjects (average age 61.4 ± 10.7 years; 82% male; body mass index 30.4 ± 5 kg/m2 ) with an average radiation dose of 12.7 mSv. On a per-vessel basis, CTP alone had a sensitivity of 79% and a specificity of 80% for the detection of stenosis ≥50%, whereas SPECT myocardial perfusion imaging had a sensitivity of 67% and a specificity of 83%. For the detection of vessels with ≥50% stenosis with a corresponding SPECT perfusion abnormality, CTP had a sensitivity of 93% and a specificity of 74%. The CTA during adenosine infusion had a per-vessel sensitivity of 96%, specificity of 73%, and negative predictive value of 98% for the detection of stenosis ≥70%. Conclusions Adenosine stress CT can identify stress-induced myocardial perfusion defects with diagnostic accuracy comparable to SPECT, with similar radiation dose and with the advantage of providing information on coronary stenosis.
Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. ...Left ventricular hypertrophy and coronary artery calcification are potent risk factors for mortality in CKD, and FGFs have been implicated in the pathogenesis of both myocardial hypertrophy and atherosclerosis. We conducted a cross-sectional study to test the hypothesis that elevated FGF-23 concentrations are associated with left ventricular hypertrophy and coronary artery calcification in patients with CKD.
In this study, 162 subjects with CKD underwent echocardiograms and computed tomography scans to assess left ventricular mass index and coronary artery calcification; echocardiograms also were obtained in 58 subjects without CKD. In multivariable-adjusted regression analyses in the overall sample, increased log FGF-23 concentrations were independently associated with increased left ventricular mass index (5% increase per 1-SD increase in log FGF-23; P=0.01) and risk of left ventricular hypertrophy (odds ratio per 1-SD increase in log FGF-23, 2.1; 95% confidence interval, 1.03 to 4.2). These associations strengthened in analyses restricted to the CKD subjects (11% increase in left ventricular mass index per 1-SD increase in log FGF-23; P=0.01; odds ratio of left ventricular hypertrophy per 1-SD increase in log FGF-23, 2.3; 95% confidence interval, 1.2 to 4.2). Although the highest tertile of FGF-23 was associated with a 2.4-fold increased risk of coronary artery calcification > or =100 versus <100 U compared with the lowest tertile (95% confidence interval, 1.1 to 5.5), the association was no longer significant after multivariable adjustment.
FGF-23 is independently associated with left ventricular mass index and left ventricular hypertrophy in patients with CKD. Whether increased FGF-23 is a marker or a potential mechanism of myocardial hypertrophy in CKD requires further study.
PDF
